Effect of a selective neuropeptide YY2 receptor antagonist, BIIE0246 on neuropeptide Y release

We have examined the selective neuropeptide Y Y-2 receptor antagonist, (S)- N-2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6 h)-oxodibenz[b,e]azepin-11-yl]-1-pipe razinyl]-2-oxoethyl]cyclopentyl]acetyl]-N-[2-[1,2-dihydro-3,5(4H)-dioxo-1,2 -diphenyl-3-H-1,2,4-triazol-4-yl]ethyl]-argininamid (BIIE0246) on neuropept ide release from rat hypothalamic slices in vitro. BIIE0246 prevented neuro peptide Y-(13-36)-induced reduction in basal and K+-stimulated neuropeptide Y release. Addition of BIIE0246 alone enhanced K+-stimulated neuropeptide release, without affecting basal release. These data are consistent with an atomical and functional studies suggesting a pre-synaptic role for neuropep tide Y Y-2 receptors in regulating rat hypothalamic neuropeptide Y release in the rat. (C) 2000 Elsevier Science B.V. All rights reserved.